Generation of muscle lineage cells and therapeutic uses thereof

Abstract

Methods and compositions for producing mature myotubes are provided herein. In some instances, the method involves contacting a myoblast in an in vitro culture with a compound, wherein the contacting the myoblast in the in vitro culture with the compound results in generation of mature myotubes or myotube-like cells. In some cases, methods of treatment are provided involving treating a subject with a compound such as a Chk1 inhibitor in order to treat muscle deficiency. The compound may be administered as a stand-alone therapy or in combination with a cell therapy, such as introduction of muscle precursor cells such as satellite cells or myoblasts. Methods for identifying compounds that induce formation of mature myotubes or myotube-like cells from myoblasts are also provided herein, as well as methods of using the identified compounds to treat subjects.

What is claimed is: 
     
       1. A composition for disease modelling, disease research and/or treatment of affected myotubes, said composition comprising a plurality of mature myotube-like cells derived from human cells, wherein a majority of the plurality of mature myotube-like cells exhibit two or more of the following features: (i) greater than 15 nuclei per mature myotube-like cell; (ii) a length greater than 0.5 mm; (iii) a diameter of at least 10 μm and (iv) a myotube area greater than 3,000 μm 2 ; wherein the plurality of mature myotube-like cells are generated by differentiating one or more myoblasts in vitro; wherein the plurality of mature myotube-like cells are generated by contacting myoblasts with a CHK1 inhibitor. 
     
     
       2. The composition of  claim 1 , wherein the CHK1 inhibitor is CHIR-124. 
     
     
       3. The composition of  claim 1 , wherein the one or more mature myotube-like cells are MyCHMyHC+, MYOG+, or both.